Mathematical cognition is critical not only for success in science and engineering but also as an important skill in everyday life, second only to reading in formal education. Recent cognitive, developmental and educational studies have provided new insights into the enduring behavioral deficits in children with mathematical learning disabilities (MLD). The development of early intervention programs is important for enhancing math learning and achievement for a broad range of children, including children who are typically developing, as well as those with developmental lags and learning disabilities. Little is known, however, about the brain and cognitive bases of MLD and the mechanisms by which these disabilities can be remediated. The overarching goal of our proposal is to investigate the brain and cognitive mechanisms that support mathematical learning and the remediation of poor mathematical skills in children with MLD. We will use a cognitive and systems neuroscience approach and state-of-the-art functional brain imaging techniques and a randomized controlled design to achieve this goal. Our study focuses on mathematical learning and skill acquisition during the ages of 7- to 9 (grades 2 and 3), a period important for learning core mathematical skills. Our proposed intervention studies will focus on three groups of children: (1) typically developing (TD) children, (2) low achieving (LA) children who lag developmentally and (3) children with MLD. We will use a randomized controlled study to investigate differences in mathematical learning and skill acquisition in these groups of children. Across the three groups, the proposed studies will: (1) elucidate the neurobiological mechanisms underlying mathematical learning, (2) provide novel insights into the role of the posterior parietal cortex, hippocampus, fusiform gyrus and prefrontal cortex in mathematical learning and remediation, (3) inform theories of mathematical cognition by characterizing the behavioral, cognitive and neural correlates of increased mathematical proficiency associated with changes in strategy use, and (4) examine reorganization and plasticity of functional brain networks with intervention. Our proposed studies will provide the first and most detailed characterization of the neurobiological underpinnings of intervention on mathematical learning in children with MLD. Findings from our study will not only have important implications for determining sources of variability in mathematical performance among LA and MLD children but also further understanding of the etiology and long-term remediation of MLD. Understanding the progression and mechanisms of mathematical development and remediating poor mathematical skills is a national priority, as emphasized by the formation of the President s National Mathematics Panel. Between 5 to 8% of children demonstrate some form of mathematical learning disability, with adverse life-long consequences for academic, vocational and professional success. Findings from our study will not only have important implications for determining mathematical learning in children, but also for understanding the cognitive and brain processes underlying mathematical learning disabilities.